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Aim To evaluate HLA-G coding and regulatory (promoter and 3’ untranslated region-3’UTR) haplotypes in papillary thyroid carcinoma (PTC) patients and their associations with clinical and histopathological features. Methods We studied 185 PTC patients and polymorphic sites distributed along the three different HLA-G gene regions were characterized by Sanger sequencing. HLA-G haplotype associations were analyzed using the Fisher exact test, calculating odds ratio (OR), confidence interval (CI) andP-values. Results More than 90 variation sites were observed along the whole gene. Considering the promoter region, i) 010101d haplotype was less frequent in patients presenting classical histological variant of PTC (OR = 0.2789, CI 95% = 0.0755–1.0304, P = 0.0499), ii) 0104a haplotype was less frequent in patients presenting tumor multicentricity (OR = 0.3360, CI 95% = 0.1446–0.7810, P = 0.0089), and iii) 0103a haplotype was more frequent in patients presenting advanced stage of PTC at diagnosis (TNM staging III and IV) (OR = 0.3541, CI 95% = 0.1360–0.9219, P = 0.0370). Regarding the coding region, the G*01:01:12(+324G) allele was associated with the presence of tumor multicentricity (OR = 11.2857, CI 95% = 1.3438–94.7784, P = 0.0094) and Hashimoto’s thyroiditis (OR = 6.4851, CI 95%=1.2383–33.9649, P = 0.0224). At 3’UTR, the UTR-02 haplotype was overrepresented (OR = 1.6759, CI 95% = 1.0616–2.6456, P = 0.0328) and UTR-03 haplotype was underrepresented (OR = 0.4106, CI 95% = 0.1912–0.8815, P = 0.0200) in patients presenting tumor multicentricity. No association regarding tumor size, local invasion, metastasis at diagnosis and extrathyroidal extension was observed. Conclusions Although HLA-G is expressed in more than 80% of PTC specimens, HLA-G alleles were primarily associated with tumor morbidity, indicating that local factors may transcriptional and posttranscriptionally modulate HLA-G expression. |
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